Osmotic Devices and Methods for Diuretic Therapy

ABSTRACT

Embodiments of the invention are related to devices and methods for modulating renal function, amongst other things. In an embodiment, the invention includes an implantable occlusive device including a wall member defining an enclosed volume, the wall member can include a semi-permeable membrane. The device can also include a solution comprising a solvent and a solute disposed within the enclosed volume of the wall member. The semi-permeable membrane can be permeable to the solvent and impermeable to the solute. The enclosed volume can be configured to expand and contract in response to changes in the osmolality of a bodily fluid. The device can include a positioning member configured to maintain the position of the implantable occlusive device relative to a lengthwise axis of a lymphatic vessel. In an embodiment, the invention includes a method of modulating renal function in a patient including implanting an occlusive device in the patient, the occlusive device comprising a semi-permeable membrane and configured to expand or contract based on the passage of a fluid across the semi-permeable membrane. Other aspects and embodiments are provided herein.

TECHNICAL FIELD

This disclosure relates generally to devices and methods for modulatingrenal function and, more particularly, to occlusive devices and methodsfor modulating renal function, amongst other things.

BACKGROUND OF THE INVENTION

The kidneys function to rid the body of metabolic and ingested wasteproducts and to maintain the volume and composition of bodily fluids.The maintenance of a constant extracellular fluid (ECF) composition bythe kidneys is accomplished by various neural, hormonal, and intrinsichomeostatic mechanisms that control the rate at which blood is filteredby the glomerulis, referred to as the glomerular filtration rate (GFR),and the extent to which sodium and water are reabsorbed from thefiltrate into the peritubular capillary blood.

The kidneys normally act to maintain both arterial blood pressure andECF volume within desired normal ranges. However, in certainpathological situations, homeostatic mechanisms do not respond in anappropriate manner. One situation in which the homeostatic mechanisms ofthe kidneys may not respond in an optimal manner is during heartfailure. Heart failure refers to a clinical syndrome in which anabnormality of cardiac function causes a below normal or normal ejectionfraction and pathophysiological ventricular hypertrophy which oftenresults in reduction in cardiac output. Such a reduction in cardiacoutput can fall below a level adequate to meet the metabolic demand ofperipheral tissues. Reduced cardiac output has a depressing effect onrenal function due to decreased renal perfusion, which causes areduction in salt and water excretion by the pressure natriuresismechanism. The renin-angiotensin-aldosterone system also promotes waterand plasma volume retention to compensate for the reduced cardiacoutput. The increased sympathetic activity in response to low bloodpressure and/or cardiac output may also depress renal function stillfurther.

The increased fluid retention by the kidneys results in an increasedblood volume and further increased venous return to the heart, thusincreasing the heart's preload. This process is acutely beneficial insupplementing and maintaining adequate cardiac output, however thisprocess can result in deleterious changes long-term. Increased fluidretention causes the progressive peripheral and pulmonary edema thatcharacterizes overt congestive heart failure. As part of downwardspiral, diastolic filling pressure becomes further elevated which causesthe heart to become so dilated and edematous that its pumping functiondeteriorates even more.

One approach to treating heart failure is to modulate renal functionthrough pharmacological means. For example, diuretic drugs can be usedto decrease the tubular reabsorption of salt and water, leading toreduced fluid retention (increased fluid excretion). However, suchpharmacological agents are not always effective and they may causesignificant side effects. In addition, patient compliance withpharmacological regimens is a serious problem.

For at least these reasons, a need exists for devices and methods formodulating renal function.

SUMMARY OF THE INVENTION

Embodiments of the invention are related to modulating renal function,amongst other things. In an embodiment, the invention includes animplantable occlusive device including a wall member defining anenclosed volume, the wall member comprising a semi-permeable membrane.The device can also include a solution comprising a solvent and a solutedisposed within the enclosed volume of the wall member. Thesemi-permeable membrane can be permeable to the solvent and impermeableto the solute. The enclosed volume can be configured to expand inresponse to decreases in osmolality of a bodily fluid and contract inresponse to increases in osmolality of a bodily fluid. The device caninclude a positioning member configured to maintain the position of theimplantable occlusive device relative to a lengthwise axis of alymphatic vessel.

In an embodiment, the invention includes a method of modulating renalfunction in a patient including implanting an occlusive device in thepatient, the occlusive device comprising a semi-permeable membrane andconfigured to expand or contract based on the passage of a fluid acrossthe semi-permeable membrane. The method can further include occluding arenal lymphatic vessel with the occlusive device.

In an embodiment, the invention includes a method of treating heartfailure decompensation including implanting an occlusive device in thepatient, the occlusive device comprising a semi-permeable membrane andconfigured to expand or contract or change its shape based on thepassage of a fluid across the semi-permeable membrane. The method canfurther include occluding a renal lymphatic vessel with the occlusivedevice.

This summary is an overview of some of the teachings of the presentapplication and is not intended to be an exclusive or exhaustivetreatment of the present subject matter. Further details are found inthe detailed description and appended claims. Other aspects will beapparent to persons skilled in the art upon reading and understandingthe following detailed description and viewing the drawings that form apart thereof, each of which is not to be taken in a limiting sense. Thescope of the present invention is defined by the appended claims andtheir legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be more completely understood in connection with thefollowing drawings, in which:

FIG. 1 is a schematic view of an occlusive device disposed within thelumen of a lymphatic vessel in accordance with an embodiment of theinvention.

FIG. 2 is a schematic view of the occlusive device of FIG. 1 in anexpanded configuration.

FIG. 3 is a schematic view of portions of the renal lymphatic system.

FIG. 4 is a schematic view of an untethered occlusive device inaccordance with an embodiment of the invention.

FIG. 5 is a cross-sectional schematic view as taken along line 5-5′ ofFIG. 4.

FIG. 6 is a schematic view of the device of FIG. 4 in a differentconfiguration.

FIG. 7 is a schematic view of an occlusive device disposed within thelumen of a lymphatic vessel in accordance with another embodiment of theinvention.

FIG. 8 is a schematic view of an occlusive device disposed within thelumen of a lymphatic vessel in accordance with another embodiment of theinvention.

FIG. 9 is a schematic view of the occlusive device of FIG. 8 is adifferent configuration.

FIG. 10 is a schematic view of an occlusive device with a sensordisposed within the lumen of a lymphatic vessel in accordance withanother embodiment of the invention.

FIG. 11 is a schematic view of a monitoring device in conjunction withan occlusive device in accordance with an embodiment of the invention.

FIG. 12 is a schematic view of some aspects of a controller inaccordance with an embodiment of the invention.

FIG. 13 is a schematic view of an occlusive device in accordance withanother embodiment of the invention.

FIG. 14 is a cross-sectional view of the occlusive device of FIG. 13 astaken along line 14-14′ of FIG. 13.

FIG. 15 is a schematic view of an occlusive device in accordance withanother embodiment of the invention.

FIG. 16 is a schematic view of an occlusive device in accordance withanother embodiment of the invention.

FIG. 17 is a schematic view of an occlusive device in accordance withanother embodiment of the invention.

FIG. 18 is a schematic view of an occlusive device in accordance withanother embodiment of the invention.

FIG. 19 is a schematic view of a multi-layer membrane structure inaccordance with an embodiment of the invention.

While the invention is susceptible to various modifications andalternative forms, specifics thereof have been shown by way of exampleand drawings, and will be described in detail. It should be understood,however, that the invention is not limited to the particular embodimentsdescribed. On the contrary, the intention is to cover modifications,equivalents, and alternatives falling within the spirit and scope of theinvention.

DETAILED DESCRIPTION OF THE INVENTION

Blocking renal lymphatic flow can modulate renal function. Specifically,blocking renal lymphatic flow can decrease fluid retention by thekidneys, or stated differently, increase the amount of fluid excretedfrom the body as urine. This diuresis is typically the goal of diureticpharmacological therapy. Embodiments of the invention can includedevices that occlude the renal lymphatic vessels, thereby blocking orreducing renal lymphatic flow. As such, embodiments of the invention canbe used to stimulate urine production and excretion by the kidneys(decrease fluid retention by the kidneys). Some embodiments can includetreating disease states, such as heart failure and/or hypertension.

Embodiments of devices included herein can include those with an elementthat changes in physical dimensions through the process of osmosis.Osmosis is a physical process in which a solvent moves, without input ofenergy, across a semi-permeable membrane (permeable to the solvent, butnot a solute) separating two solutions having different soluteconcentrations. Net movement of solvent is from the less-concentrated(hypotonic) solution, to the more-concentrated (hypertonic) solution.

Referring now to FIG. 1, a schematic view is shown of an occlusivedevice 100 disposed within the lumen 114 of a renal lymphatic vessel 108in accordance with an embodiment of the invention. A wall member 102including a semi-permeable membrane encloses an enclosed volume 106. Thewall member 102 is attached to a lead member 104 or tether. The leadmember 104 can serve to maintain the position of the occlusive device100 within the lymphatic vessel 108. The lead member 104 can serve asone example of a positioning member since it can serve to maintain theposition of the occlusive device relative to the lengthwise axis of thelymphatic vessel (axis of fluid flow) in which it can occlude fluidflow. The lengthwise axis of the renal lymphatic vessel 108 is indicatedby arrowed line 101.

A solution including a solvent and a solute is disposed within theenclosed volume 106. In some embodiments, the solvent is water. Thesolute can include many different types of chemical compounds. In anembodiment, the solute is a biocompatible chemical compound. In anembodiment, the solute is a chemical compound naturally occurring withinthe body. In an embodiment, the solute is sodium chloride. In anembodiment, the solute is glucose. Further examples of solutes aredescribed below.

The enclosed volume 106 can change in size as a result of osmosis.Specifically, where the solution within the enclosed volume 106 has ahigher osmolality than the bodily fluid within the lumen 114 of thelymphatic vessel 108, fluid can diffuse across the semi-permeablemembrane and into the enclosed volume 106, causing the same to enlarge.Conversely, where the solution within the enclosed volume 106 has alower osmolality than the bodily fluid within the lumen 114 of thelymphatic vessel 108, fluid can diffuse across the semi-permeablemembrane and out of the enclosed volume 106, causing the same to becomesmaller. Between about 280 and 303 mOsm/kg is a normal value ofosmolality in fluids of the body. As such, in some embodiments, thesolution within the enclosed volume has a starting osmolality of betweenabout 280 and 303 mOsm/kg when the device is implanted within a patient.In other embodiments, the solution within the enclosed volume can have astarting osmolality outside of that range.

Though units of osmolality are used herein to describe concentrations ofsolutions, it will be appreciated that units of osmolarity could also beused.

In some embodiments, the enclosed volume 106 can swell from a firstdiameter 110 to a second diameter 112. The closer the enclosed volume106 approaches the size of the lymphatic vessel lumen 114, the more itoccludes the flow of fluid through the renal lymphatic vessel 108.Complete or partial occlusion of the lymphatic vessel lumen 114 canresult in modulating renal function so as to excrete more fluid,achieving a result similar to the administration of diuretic therapeuticagents.

Referring now to FIG. 2, a schematic view of the occlusive device ofFIG. 1 is shown in an expanded configuration. In this view, the enclosedvolume 106 is expanded to a degree that the occlusive device 100 is nowoccluding substantially the entire lumen 114 of the renal lymphaticvessel 108. It will be appreciated that the device 100 can be configuredso that maximal expansion of the enclosed volume 106 occludes aparticular percentage of the lumen of the renal lymphatic vessel 108.For example, in some embodiments, the device can be configured so thatit occludes a maximum of approximately 50% of the cross-sectional areaof the lumen 114 of the renal lymphatic vessel when the enclosed volume106 is fully expanded. In some embodiments, the device can be configuredso that it occludes a maximum of approximately 70% of thecross-sectional area of the lumen 114 of the renal lymphatic vessel whenthe enclosed volume 106 is fully expanded. In some embodiments, thedevice can be configured so that it occludes a maximum of approximately90% of the cross-sectional area of the lumen 114 of the renal lymphaticvessel when the enclosed volume 106 is fully expanded. In someembodiments, the device can be configured so that it occludesapproximately 100% of the cross-sectional area of the lumen 114 of therenal lymphatic vessel when the enclosed volume 106 is fully expanded.

Occlusive devices in accordance with embodiments of the invention can beplaced into various locations in the body in order to modulate renalfunction. Referring now to FIG. 3, a schematic view is shown of portionsof the renal lymphatic system. FIG. 3 shows a right kidney 152 and aleft kidney 154. Renal lymphatic vessels 158 can emerge from the kidneynear the Hilar region 156 of the kidney. The renal lymphatic vessels 158can serve to carry lymphatic fluid. The renal lymphatic vessels 158 canjoin together to form a renal lymphatic vessel trunk 160. The renallymphatic vessel trunk 160 passes the lymphatic fluid on to the thoracicduct 162. One or more occlusive devices, as described herein, can bepositioned appropriately to block or reduce the flow of lymphatic fluidthrough the renal vessels including individual vessels 158 and thevessel trunk 160 as well as the thoracic duct 162 itself. As usedherein, the term “renal lymphatic vessel” shall include both theindividual vessels and the vessel trunk. The occlusive devices can beplaced inside of or adjacent to the individual vessels 158 or the trunk160. In some embodiments, an occlusive device can be positioned on orwithin the thoracic duct 162.

In some embodiments, the occlusive device can be untethered. Forexample, the occlusive devices themselves can include a retention memberto maintain their position within the lumen of a renal lymphatic vessel.Referring now to FIG. 4, an embodiment of an untethered occlusive device200 is shown in accordance with an embodiment of the invention. Theocclusive device 200 includes a wall member 202 that includes asemi-permeable membrane. The wall member 202 surrounds an enclosedvolume 206, separating the enclosed volume 206 from the lumen 214 of therenal lymphatic vessel 208. A retention member 216 can be coupled to thewall member 202. The retention member 216 can be configured to engagethe inside surfaces 209 of the renal lymphatic vessel 208. The retentionmember 216 can include one or more arms 217 or appendages.

Referring now to FIG. 5, a cross-sectional schematic view of the renallymphatic vessel is shown as taken along line 5-5′ of FIG. 4. In thisview, the retention member 216 can be seen engaging the inside surface209 of the renal lymphatic vessel 208. In some embodiments, theretention member 216 can be configured so that it exerts a force againstthe inside surface 209 of the renal lymphatic vessel 208.

Referring now to FIG. 6, the retention member 216 can exhibit a degreeof elasticity so that the arms 217 or appendages of the retention member216 can be disposed against the wall member 202 to facilitate insertingthe occlusive device 200 into a desired location within the renallymphatic vessel system. For example, a sheath (not shown) can bedisposed over the arms 217 when the occlusive device 200 is beinginserted into the proper position. In this configuration, the effectivediameter of the retention member is smaller than the diameter of thelumen 214. Then, after the occlusive device has been maneuvered into thedesired position, the sheath can be removed allowing the arms 217 toflex outwardly and engage the inside surface 209 of the renal lymphaticvessel 208.

The retention member 216 can include many different materials. By way ofexample, the retention member 216 can include polymers, metals, metalalloys, ceramics, and the like. In some embodiments, the retentionmember 216 is a shape memory material, such as a shape memory metal. Inan embodiment, the retention member 216 is the alloy nitinol. In theembodiment shown in FIGS. 4-6, the retention member 216 has two arms.However, it will be appreciated that in other embodiments the retentionmember can have a different number of arms. By way of example, theretention member can include three arms, four arms, or more than fourarms. It will be appreciated that the retention member can also take ondifferent shapes. By way of example, in some embodiments, the retentionmember can have a substantially annular shape. The retention member canalso include a tubular mesh configuration similar to shape of vascularstents. The retention member can serve as an example of a positioningmember since it can serve to maintain the position of the occlusivedevice relative to the lengthwise axis of the renal lymphatic vessel(axis of fluid flow) in which it can occlude fluid flow.

In some embodiments, the wall member of the occlusive device can includea non-permeable membrane (non-permeable to both solvents and solutes) inaddition to the semi-permeable membrane. For example, the wall membercan include a semi-permeable membrane in areas where it is desired tohave fluids diffuse through and can include a non-permeable membrane inother areas. In some embodiments, a non-permeable portion of the wallmember can be used to enhance the structural characteristics of thedevice. In addition, a non-permeable portion of the wall member can beused to control how the enclosed volume of the occlusive device expands,such as the direction in which it expands.

Referring now to FIG. 7, a schematic view is shown of an occlusivedevice disposed within the lumen 314 of a lymphatic vessel 308 inaccordance with another embodiment of the invention. A wall member 302including a semi-permeable membrane encloses an enclosed volume 306. Thewall member 302 is attached to a lead member 304. The lead member canserve to maintain the position of the occlusive device. A solutionincluding a solvent and a solute is disposed within the enclosed volume306. The wall member 302 can include a non-permeable portion 318 orpatch (impermeable to both the solvent and the solute). In someembodiments, the non-permeable portion 318 is joined at its perimeter tothe semi-permeable membrane. In some embodiments, the non-permeableportion 318 is disposed on top of the semi-permeable membrane. In someembodiments, the non-permeable portion 318 is adhered to thesemi-permeable membrane, such as with an adhesive. In some embodiments,the non-permeable portion 318 is welded to the semi-permeable membrane.

In some applications it may be desirable to ensure that some percentageof the lymphatic vessel remains open to the flow of lymphatic fluid. Assuch, in some embodiments, an occlusive device can include a centrallumen or channel that provides a passageway for lymphatic fluid,regardless of the state of expansion of the occlusive device. Referringnow to FIG. 8, an embodiment of an occlusive device 350 with a channelis shown disposed within the lumen 364 of a lymphatic vessel 358 inaccordance with an embodiment of the invention. A wall member 352including a semi-permeable membrane encloses an enclosed volume 356. Asolution including a solvent and a solute is disposed within theenclosed volume 356.

The wall member 352 is coupled to a channel member 362 defining a devicelumen 366. The channel member 362 can include a cylindrical-type shape,resisting deformation when the enclosed volume 356 expands andcontracts. For example, the channel member 362 can include a polymericor metallic tube. The device lumen 366 can serve as a passageway forlymphatic fluid regardless of the degree of expansion of the enclosedvolume 356. Referring now to FIG. 9, the occlusive device 350 of FIG. 8is shown in an expanded configuration. In this view it can be seen thatenclosed volume 356 has expanded to the bounds of the interior of thelymphatic vessel 358 and that the device lumen 366 still provides apassageway for lymphatic fluid. The device lumen 366 can have across-sectional area as large as is desired for the specificapplication. In some embodiments, the device lumen 366 includes across-sectional area equal to at least about 5% of the totalcross-sectional area of the lumen 364 of the lymphatic vessel 358. Insome embodiments, the device lumen 366 includes a cross-sectional areaequal to at least about 10% of the total cross-sectional area of thelumen 364 of the lymphatic vessel 358.

In some circumstances, it can be desirable to monitor the status of theocclusive device in vivo. In some embodiments, the occlusive deviceincludes a sensor so that the status and degree of expansion of theocclusive device can be monitored. Referring now to FIG. 10, anocclusive device with a sensor 420 is shown disposed within the lumen414 of a lymphatic vessel 408 in accordance with another embodiment ofthe invention. A wall member 402 including a semi-permeable membraneencloses an enclosed volume 406. A solution including a solvent and asolute is disposed within the enclosed volume 406. A sensor 420 can bein communication with the enclosed volume 406. The wall member 402 iscoupled to a lead member 404. The lead member 404 can serve to maintainthe position of the occlusive device. The lead member 404 can alsoinclude an electrical or an optical conductor in order to convey signalsto or from the sensor 420.

The sensor 420 can be configured to sense various properties that areindicative of the status and performance of the occlusive device. Insome embodiments, the sensor 420 can be configured to sense pressurewithin the enclosed volume 406 of the occlusive device. The sensor 420can include any type of pressure sensor, for example an electrical,mechanical, or optical pressure sensor, that generates a signal inresponse to pressure. By way of example, exemplary pressure sensors aredescribed in U.S. Pat. No. 6,237,398, the content of which is hereinincorporated by reference.

In some embodiments, the sensor 420 can be configured to sense theosmolality within the enclosed volume 406. Generally, it is expectedthat the osmolality within the enclosed volume 406 will reflect theosmolality of the bodily fluid surrounding the occlusive device sincefluid can diffuse through the semi-permeable membrane in order toequalize osmolalities. However, sudden large changes in osmolality canbe indicative of dysfunction of the patient or of the device itself. Assuch, in some embodiments, signals from the sensor 420 can pass throughthe lead member 404 to a monitoring device which can be configured tomonitor for changes in sensed osmolality. Many different types ofosmolality sensors can be used. One example of an osmolality sensor isdescribed in U.S. Pat. No. 5,388,449, the contents of which is hereinincorporated by reference.

In some embodiments, the sensor 420 can be configured to sense thephysical dimensions of enclosed volume 406. For example, the sensor 420can be configured to sense the diameter of the enclosed volume 406and/or the length of the enclosed volume 406. Specifically, the sensor420 can include photosensor with a light source, such as a lightemitting diode (LED), and a light receiver, such as a charge-coupleddevice (CCD), photodiode, a junction field effect transistor (JFET) typeoptical sensor, or a complementary metal-oxide semiconductor (CMOS) typeoptical sensor. The light source can generate an emission of lightwithin the enclosed volume 406 that reflects off an opposing part of thewall member before being received by the light receiver. The larger thesize of the enclosed volume 406, the farther the light must travel andthe greater the loss of light intensity due to diffusion. Therefore, theintensity of light received by the light receiver can be correlated tothe size of the enclosed volume. It will be appreciated that this ismerely one example of a sensor for detecting the physical dimensions ofthe enclosed volume and that there are also many other types of sensorsthat can also be used to sense the size of the enclosed volume.

In some embodiments, signals from the sensor can pass through the leadmember to a monitoring device. Referring now to FIG. 11 a schematic viewof a system 500 including a monitoring device 530 in conjunction with anocclusive device 502 is shown in accordance with an embodiment of theinvention. The monitoring device 530 can include a controller module532. The monitoring device 530 can be coupled to a lead 504 which is inturn coupled to an occlusive device 502 that includes a sensor. However,it will be appreciated that in some embodiments, the monitoring device530 and the occlusive device 502 can be in wireless communication.

A remote monitoring device 534 can also be included and can be inwireless communication with the monitoring device 530. For example, dataregarding the occlusive device 502, as stored by the controller 532, canbe wirelessly transmitted to the remote monitoring device 534. Theremote monitoring device 534 can be a patient management system. Anexemplary patient management system includes the LATITUDE® patientmanagement system, commercially available from Boston ScientificCorporation, Natick, Mass. Aspects of an exemplary patient managementsystem are described in U.S. Pat. No. 6,978,182, the contents of whichare herein incorporated by reference.

The controller 532 can include various electronic components and can beconfigured to process signals from a sensor within an occlusive device,including analyzing the signals and storing data regarding the signals.Referring now to FIG. 12, some aspects of a controller 532 areschematically illustrated. In this embodiment, the controller 532includes a microprocessor 552 that communicates with memory 554 via abidirectional data bus. The memory 554 typically comprises ROM or RAMfor program storage and a RAM for data storage. The controller 532 caninclude a bidirectional occlusive device sensor channel interface 556.In addition, the controller 532 can include a clock circuit 562. Thecontroller 532 can also include a telemetry interface module 564 forwireless communication of data into and out of the controller 532.

In some embodiments, the invention can include occlusive devicesconfigured to be disposed on the outside of renal lymphatic vessels.Referring now to FIG. 13, an embodiment of an occlusive device is shownin accordance with another embodiment of the invention. The occlusivedevice can include a wall member 602 defining an enclosed volume 606(shown in FIG. 14). The wall member 602 can include a semi-permeablemembrane, examples of which are described in greater detail below. Asemi-rigid support member 622 can be disposed around the outer perimeterof the wall member 602. The semi-rigid support member 622 can serve tomaintain the occlusive device in position around the renal lymphaticvessel 608. The semi-rigid support member 622 can also serve as anexample of a positioning member since it can serve to maintain theposition of the occlusive device relative to the lengthwise axis of therenal lymphatic vessel 608 (axis of fluid flow) in which it can occludefluid flow.

In some embodiments, the wall member 602 and the semi-rigid supportmember 622 can both have a shape similar to a ring with a gap 624 in theperimeter of the ring. This shape can also be referred to as adiscontinuous annular shape. The occlusive device can be wrapped arounda renal lymphatic vessel 608. The gap 624 in the wall member 602 and thesemi-rigid support member 622 can allow the ring-shaped device to beopened so that it can be positioned around the renal lymphatic vessel608.

Referring now to FIG. 14, a cross-sectional view of the occlusive deviceof FIG. 13 is shown as taken along line 14-14′ of FIG. 13. As thesupport member 622 is semi-rigid, it serves to direct expansion of theenclosed volume 606 inward toward the lumen 614 of the renal lymphaticvessel 608. In some embodiments, the support member can be made of apolymer or a metal.

However, some embodiments of occlusive devices configured to be disposedoutside of renal lymphatic vessels can lack support members. Forexample, referring now to FIG. 15, an embodiment of an occlusive deviceis shown lacking a support member. The occlusive device can include awall member 702 defining an enclosed volume. The wall member 702 caninclude a semi-permeable membrane, examples of which are described ingreater detail below. The occlusive device can be wrapped around a renallymphatic vessel 708. A gap 724 in the wall member 706 can allow thedevice to be opened so that it can be wrapped around the renal lymphaticvessel 708.

In some embodiments, the enclosed volume of the occlusive device can befilled with a solution including a solvent and a solute when the deviceis first manufactured. For example, in some embodiments, a solution withan osmolality of between about 280 and about 303 mOsm/kg is disposedwithin the enclosed volume when the device is initially manufactured.However, in other embodiments, the device can be configured so that itcan be filled up with a solution having a desired solute concentrationjust before insertion into the patient. For example, in general, the useof solutions with higher concentrations of solute will result in greaterinitial swelling or enlargement of the enclosed volume of the deviceafter it is positioned within the patient. As such, in some embodiments,the solute concentration of the solution can be manipulated by theclinician before implantation. For example, if the device is to bedisposed within or around a particularly large renal lymphatic vessel,the starting osmolality of the solution within the enclosed volume canbe increased so that there will be greater initial swelling orenlargement of the occlusive device. However, in other circumstances,where a smaller size is desired, a solution with a lesser concentrationof solute can be inserted into the device before implantation into apatient. In some embodiments, a kit is provided including an occlusivedevice as described herein and a set of solutions with different soluteconcentrations, from which a health professional can select for use.

Referring now to FIG. 16, an embodiment of an occlusive device with aninjection port is shown. The occlusive device can include a wall member802 defining an enclosed volume. The wall member 802 can include asemi-permeable membrane, examples of which are described in greaterdetail below. A semi-rigid support member 822 can be disposed around theouter perimeter of the wall member 802. An injection port 826 can bedisposed on the wall member 802. The injection port 826 can allow asyringe 828 to be inserted into the device to deliver a solution intothe enclosed volume of the device. The injection port 826 can include aplug of material that self-seals to prevent leakage once the needle ofthe syringe 828 is withdrawn. For example, in an embodiment theinjection port 826 can include a polymer with elastomeric properties. Inan embodiment, the injection port 826 can include a polysiloxanepolymer.

In some embodiments, an occlusive device can be disposed adjacent to arenal lymphatic vessel and can be configured to expand in a directionthat results in occlusion of the renal lymphatic vessel. Referring nowto FIG. 17, an occlusive device 850 is shown in accordance with anotherembodiment of the invention. The occlusive device 850 can include a wallmember 852 defining an enclosed volume. The wall member 852 can includea semi-permeable membrane, examples of which are described in greaterdetail below. A semi-rigid support member 876 can be disposed around theinner perimeter of the wall member 852. In some embodiments, thesemi-rigid support member 876 can include a semi-permeable membrane. Theocclusive device 850 can be wrapped around a first vessel 858, whichcould be any type of vessel-like structure such as an artery or a vein.The enclosed volume can expand in the direction of arrow 878 as a resultof changes in osmolality in the bodily fluid surrounding the device 850.Expansion can occur to an extent that the device 850 exerts a force onan adjacent renal lymphatic vessel 880 and occludes the same. Thesemi-rigid support member 876 can prevent expansion of the enclosedvolume from occluding the first vessel 858 and focus expansion in anoutward direction. A harness 882 or strap can be included so as toprevent the adjacent renal lymphatic vessel 880 from simply moving awaywhen the device 850 expands. The harness 882 can include a loop ofmaterial wrapped around the adjacent renal lymphatic vessel 880. Theharness 882 can also serve as an example of a positioning member sinceit can serve to maintain the position of the occlusive device relativeto the lengthwise axis of the lymphatic vessel (axis of fluid flow) inwhich it can occlude fluid flow.

In some cases, it may be desirable to configure the device to be moredirectly responsive to changes in osmolality within arteries and/orveins. In some embodiments, the occlusive device can include a fingerlike projection or protruding member that passes from a wall member,through an aperture in the wall of an artery or vein, and into theinterior lumen of the artery or vein. The projection can include asemi-permeable membrane and can be in fluid communication with anenclosed volume of the occlusive device. In some embodiments, otherportions of the occlusive device are impermeable. As such, expansion andcontraction of the occlusive device can be made to be particularlysensitive to changes in osmolality in plasma within the lumen of anartery or vein.

In some embodiments, over-expansion of the device can be controlled forpurposes of safety. Various techniques and structures can be used toprevent over-expansion. For example, in an embodiment, an inflexibleband can be disposed over the device, the inflexible band having acircumference corresponding to the maximum allowable size of theocclusive device. In another embodiment, the device can include apressure release valve, the valve configured to open when a certainthreshold pressure is reached inside of the occlusive device. Referringnow to FIG. 18, an embodiment of an occlusive device with a pressurerelease valve is shown. The occlusive device can include a wall member902 defining an enclosed volume. The wall member 902 can include asemi-permeable membrane, examples of which are described in greaterdetail below. A pressure release valve 926 can be disposed on the wallmember 902. The pressure release valve 926 can be configured to openwhen the pressure in the area enclosed by the wall member 902 exceeds athreshold amount. As such, the pressure inside of the enclosed volume isprevented from becoming so high that the wall member 902 could ruptureor that the area enclosed by the wall member 902 becomes undesirablylarge. Many different types of pressure release valves 926 are known tothose of skill in the art and can be used.

Semi-Permeable Membranes

Embodiments of the invention can include a semi-permeable membrane. Theterm “semi-permeable membrane” as used herein shall refer to a membranethat is permeable to a solvent but impermeable to one or more solutes,such that the semi-permeable membrane can be used in the process ofosmosis. Exemplary solutes can include chemical compounds found withinbodily fluids such as salts and their ions including calcium ions,sodium ions, potassium ions, chlorine ions, glucose and othercarbohydrates, proteins (such as albumin), glycosaminoglycans, and thelike. The term “impermeable” as applied to an article, such as amembrane, shall refer to one that substantially blocks the passage ofone or more compounds through its substance.

It will be appreciated that semi-permeable membranes can be constructedof many different types of materials. For example, semi-permeablemembranes can include polymers such as cellulose, cellulose derivatives,polyacrylonitrile, polysulfone, polycarbonates, polyamides,polymethylmethacrylate (PMMA), polyethylenes, polytetrafluoroethylene(PTFE), and polysiloxanes. In some embodiments, the semi-permeablemembrane can include a hydrogel. The specific choice of material candepend on factors such as desired tear strength, desired flexibility,and the like. In an embodiment, the semi-permeable membrane includes abiocompatible material.

In some embodiments, the semi-permeable membrane can be porous. Thepores can have a diameter large enough to allow for the passage of watermolecules but small enough to prevent the passage of various solutesfound in bodily fluids.

The semi-permeable membrane can have a thickness that is sufficient toprovide strength to prevent tearing under the conditions of use.However, the semi-permeable membrane can be thin enough to maintainflexibility. In some embodiments, the semi-permeable membrane is betweenabout 1 nanometer and about 2 millimeters in thickness. In someembodiments, a semi-permeable membrane can include multiple layers ofmaterial. For example, referring to FIG. 19, an embodiment of amulti-layer semi-permeable membrane 950 structure is shown. A firstlayer 972 is disposed beneath a second layer 974. The first layer 972and second layer 974 can include the same materials or differentmaterials. In some embodiments, the first layer 972 is fastened to thesecond layer 974. For example, an adhesive can be disposed between thefirst layer 972 and the second layer 974. In some embodiments, the firstlayer 972 and the second layer 974 are thermally welded together, suchas through ultrasonic welding or a similar technique.

In some embodiments, the semi-permeable membrane can have an irregularlyshaped surface or various types of surface features such as dimples inorder to increase its effective surface area.

It should be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the content clearly dictates otherwise. It should also be notedthat the term “or” is generally employed in its sense including “and/or”unless the content clearly dictates otherwise.

It should also be noted that, as used in this specification and theappended claims, the phrase “configured” describes a system, apparatus,or other structure that is constructed or configured to perform aparticular task or adopt a particular configuration. The phrase“configured” can be used interchangeably with other similar phrases suchas “arranged”, “arranged and configured”, “constructed and arranged”,“constructed”, “manufactured and arranged”, and the like.

All publications and patent applications in this specification areindicative of the level of ordinary skill in the art to which thisinvention pertains. All publications and patent applications are hereinincorporated by reference to the same extent as if each individualpublication or patent application was specifically and individuallyindicated by reference.

This application is intended to cover adaptations or variations of thepresent subject matter. It is to be understood that the abovedescription is intended to be illustrative, and not restrictive. Thescope of the present subject matter should be determined with referenceto the appended claims, along with the full scope of equivalents towhich such claims are entitled.

1. An implantable occlusive device comprising: a wall member defining anenclosed volume, the wall member comprising a semi-permeable membrane; asolution comprising a solvent and a solute, the solution disposed withinthe enclosed volume; and a positioning member, the positioning memberconfigured to maintain the position of the implantable occlusive devicerelative to a lengthwise axis of a lymphatic vessel; the semi-permeablemembrane permeable to the solvent and impermeable to the solute; theenclosed volume configured to expand in response to decreases inosmolality of a bodily fluid and contract in response to increases inosmolality of a bodily fluid.
 2. The implantable occlusive device ofclaim 1, the semi-permeable membrane comprising a biocompatiblematerial.
 3. The implantable occlusive device of claim 1, the solutecomprising at least one of sodium chloride and potassium chloride. 4.The implantable occlusive device of claim 1, the semi-permeable membranecomprising a polymer.
 5. The implantable occlusive device of claim 4,the semi-permeable membrane comprising polytetrafluoroethylene.
 6. Theimplantable occlusive device of claim 1, the wall member comprising amembrane impermeable to both the solvent and the solute.
 7. Theimplantable occlusive device of claim 1, the positioning membercomprising a rigid support member disposed around an outer perimeter ofthe enclosed volume.
 8. The implantable occlusive device of claim 7, therigid support member comprising an annular shape.
 9. The implantableocclusive device of claim 1, further comprising an osmolality sensorconfigured to sense the osmolality of the solution within the enclosedvolume.
 10. The implantable occlusive device of claim 1, furthercomprising a pressure sensor configured to sense the pressure within theenclosed volume.
 11. The implantable occlusive device of claim 1, thepositioning member comprising a lead body coupled to the wall member.12. The implantable occlusive device of claim 11, further comprising aconductor disposed within the lead body.
 13. The implantable occlusivedevice of claim 1, the positioning member comprising one or moreappendages configured to engage an inside surface of a renal lymphaticvessel.
 14. A method of modulating renal function in a patientcomprising: implanting an occlusive device in the patient, the occlusivedevice comprising a semi-permeable membrane, the occlusive deviceconfigured to expand or contract based on the passage of a fluid acrossthe semi-permeable membrane; and occluding a renal lymphatic vessel withthe occlusive device.
 15. The method of claim 14, comprising implantingthe occlusive device inside a renal lymphatic vessel of the patient. 16.The method of claim 14, comprising implanting the occlusive deviceoutside of a renal lymphatic vessel of the patient.
 17. The method ofclaim 14, the occlusive device configured to expand in response todecreases in osmolality of a bodily fluid.
 18. The method of claim 14,the occlusive device configured to expand in response to decreases inosmolality of a bodily fluid within a renal lymphatic vessel.
 19. Themethod of claim 14, the occlusive device configured to contract inresponse to increases in osmolality of a bodily fluid.
 20. The method ofclaim 14, the occlusive device configured to contract in response toincreases in osmolality of a bodily fluid within a renal lymphaticvessel.
 21. The method of claim 14, the occlusive device defining anenclosed volume.
 22. The method of claim 21, further comprisinginserting a solution comprising a solvent and a solute into the enclosedvolume.
 23. A method of treating a hypervolemic state including heartfailure decompensation and/or hypertension comprising: implanting anocclusive device in the patient, the occlusive device comprising asemi-permeable membrane, the occlusive device configured to expand orcontract based on the passage of a fluid across the semi-permeablemembrane; and occluding a renal lymphatic vessel with the occlusivedevice.